Pluripotent Adipose Stem Cell Isolation for Tissue Regeneration

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Solution Overview

Problem

Current stem cell therapies face limitations due to high rates of immunorejection, teratoma formation, and ethical concerns with embryonic stem cells, while induced pluripotent stem cells have low survival rates and epigenetic memory issues, hindering their clinical application for tissue regeneration.

Innovation Solution

The isolation and use of pluripotent adipose stem cells (PASCs) from adipose tissue through stress conditions such as proteolytic enzyme treatment, hypoxia, and co-culturing, which allows for a high-purity population without the need for cell sorting or prolonged cell culture, enabling efficient tissue regeneration without teratoma formation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If embryonic stem cells are used for tissue regeneration, then the potential to treat irreversible disorders is improved, but immunorejection rates and teratoma formation increase

Engineering Contradiction:

Improvetissue regeneration efficacyVSAvoidimmunorejection and teratoma formation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and isolates pluripotent stem cells specifically from the adipose tissue stromal vascular fraction, separating them from other cell types through density gradient centrifugation and magnetic bead sorting. This extraction process obtains the desired pluripotent cells while leaving behind the harmful factors associated with embryonic stem cells, achieving tissue regeneration without immunorejection and teratoma formation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses adipose tissue as an intermediary source between embryonic stem cells and adult stem cells. The adipose-derived pluripotent cells serve as a mediator that provides the regenerative capacity of embryonic stem cells while avoiding their immunogenicity and tumorigenicity, effectively bridging the gap between high potency and safety

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If induced pluripotent stem cells are used to avoid ethical issues, then ethical concerns are resolved, but survival rates remain extremely low

Engineering Contradiction:

Improveethical acceptabilityVSAvoidpost-transplantation survival rate

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the source parameter from reprogrammed somatic cells to naturally occurring pluripotent cells in adipose tissue. By harvesting cells that are already pluripotent in their native state rather than reprogramming them, the method achieves high post-transplantation survival rates while maintaining ethical acceptability, as no genetic manipulation or reprogramming is required

Inventive Principle:

Principle #35Parameter changes

3Manufacturing precision

If cell sorting methods are used to obtain pure stem cell populations, then purity is improved, but time and complexity increase

Engineering Contradiction:

Improvestem cell population purityVSAvoidisolation procedure duration

Core Design Contradiction:

Manufacturing precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary enrichment of pluripotent stem cells in the stromal vascular fraction before final isolation. By pre-sorting for CD34+ cells using magnetic beads and performing density gradient centrifugation first, the subsequent purification steps require less time and fewer operations to achieve the desired purity, reducing overall isolation time while maintaining high purity levels

Inventive Principle:

Principle #10Preliminary action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

PASCs demonstrate high survival rates, efficient tissue regeneration, and integration into damaged sites, overcoming previous limitations by providing a non-tumorigenic, autologous transplantation method with improved post-transplantation survival and reduced immunorejection.

Implementation Method 1

subjecting cells in said sample to stress conditions... The stress conditions of step (b) comprise incubating the cells in a medium containing a proteolytic enzyme

Methodology Applied

Scientific EffectProteolytic enzyme treatment: Enzyme

Implementation Method 2

subjecting cells in said sample to stress conditions... (c) co-culturing adipocytes and a stromal vascular fraction for 2-36 hours

Methodology Applied

Scientific EffectHypoxia:

Data Source

PatentUS20240076623A1Methods of treatment using pluripotent human adipose adult stem cells

Publication Date: 2024.03.07 RGT UNIV OF CALIFORNIA

AI summary

Methods for the efficient isolation and use of pluripotent adipose-derived stem cells (PASCs) are provided. In certain embodiments the methods involve providing an adipose tissue sample from which the stromal vascular fraction is co-cultured with the adipocyte fraction. PASCs can be isolated with a high degree of purification without requiring an additional cell enrichment process (e.g. cell sorting). PASCs and their conditioned media can be used for tissue regeneration within hours of harvesting the adipose tissue, and without requiring cell expansion. PASCs can grow as floating individual cells, as clusters of cells, or attached to surface(s) of the culture vessel. PASCs do not produce teratomas in vivo, nor do they induce immunorejection upon transplantation, and they achieve a high efficiency in grafting. The cells and compositions can be used for cell therapy and to screen new drugs.